meta-Selective C–H functionalisation of aryl boronic acids directed by a MIDA-derived boronate ester

Abstract

N-Methyliminodiacetic acid (MIDA) boronates are boronic acid derivatives which are stable to reduction, oxidation and transmetalation. This has led to their widespread use as boronic acid protecting groups (PGs) and in iterative cross-couplings. We describe herein the development of a novel MIDA derivative that acts in a dual manner, as a protecting group and a directing group (DG) for meta C(sp 2 )-H functionalisation of arylboronic acids. Palladium catalysed C-H alkenylations, acetoxylations and arylations are possible, at room temperature and under aerobic conditions. Deprotection to reveal the functionalised boronic acids is rapid and allows for full recovery of the DG. The technique allows the facile diversification of aryl boronic acids and their subsequent use in a range of reactions or in iterative processes.Scheme 4 Deprotection and derivatisation of C-H functionalised aryl MIDA-DG boronate. The boronic acid was used directly after deprotection without purification. All yields given are over two steps.

Toolbox for Distal C–H Bond Functionalizations in Organic Molecules

“…Recently, Spivey, Cordiar, and co-workers developed boronic acid derivatives as protecting and directing groups for meta -C–H functionalization . Under room temperature conditions, palladium-catalyzed alkenylation, acetoxylation and arylation was possible on such substrates.…”

Recent development in transition metal-catalysed C–H olefination

“…Recently, Spivey, Cordier and co-workers presented a novel N -methyl iminodiacetic acid (MIDA) boronate derivative as the protecting cum directing group for the Pd-catalysed meta- selective olefination of boronic acids 92 ( Scheme 45 ). 53 MIDA-DG boronate could be easily accessed through condensation with boronic acid and also can be removed under mild basic conditions. The reaction tolerated a series of substituted phenylboronic acids and activated olefins to give meta -olefinated products 93 in moderate yield and selectivity.…”

Synthesis of Benzoxaboroles by ortho-Oxalkylation of Arylboronic Acids with Aldehydes/Ketones in the Presence of Brønsted Acids

“…It is clear that benzoxaboroles can be regarded as the intramolecular dehydration product of ortho -hydroxyalkyl-substituted arylboronic acids ( H ). In consideration of the atom economy, an ideal method to obtain H is the direct ortho -hydroxyalkylation of arylboronic acids with aldehydes or ketones; however, arylboronic acids are highly reactive, and only a few types of functionalization of arylboron compounds have been previously reported, and most of them deal with halogenations and nitration …”